directly on rotatable bonds whereas the nonbonding potentials do not.

A question that is invariably asked about the conformational database potential is whether one will be able to pick up unusual sidechain or backbone conformations. Inspection of high resolution protein x-ray structures indicates that one safely can assume that 90–95% of all residues have a sidechain conformation resembling that of a common rotamer (50). Under these conditions, residues that truly exhibit a skewed rotamer conformation will be spotted by specific discrepancies between the model and the experimental restraints, and in most circumstances such violations will be accounted for by special structural features of the model. Moreover, one should be especially careful in believing a nonrotamer sidechain conformation in NMR structures in the absence of extensive NOE and coupling constant data relating to that particular residue. Exactly the same arguments can be applied to ϕ, ψ angles located in unfavorable regions of the Ramachandran plot, which likewise should be treated with extreme caution unless there is extensive experimental evidence to the contrary (50).

We thank Ad Bax, Dan Garrett, John Kuszewski, and Nico Tjandra for many stimulating discussions.

1. Clore, G.M. & Gronenborn, A.M. (1991) Science 252, 1390– 1399.

2. Wuthrich, K. (1986) NMR of Proteins and Nucleic Acids (Wiley, New York).

3. Clore, G.M. & Gronenborn, A.M. (1987) Protein Eng. 1, 275–288.

4. Dyson, H.J., Gippert, G.P., Case, D.A., Holmgren. A. & Wright, P.E. (1990) Biochemistry 29, 4129–4136.

5. Forman-Kay, J.D., Clore, G.M., Wingfield, P.T. & Gronenborn, A.M. (1991) Biochemistry 30, 2685–2698.

6. Clore, G.M., Wingfield, P.T. & Gronenborn, A.M. (1991) Biochemistry 30, 2315–2323.

7. Clore, G.M. & Gronenborn, A.M. (1991) J. Mol. Biol. 221, 47–53.

8. Garrett, D.S., Seok, Y.J., Liao, D.-I., Peterkofsky, A., Gronenborn, A.M. & Clore, G.M. (1997) Biochemistry 36, 2517–2530.

9. Martin, J.R., Mulder, F.A.A., Karimi-Nejad, Y., van der Zwan, J., Mariani, M., Schipper, D. & Boelens, R. (1997) Structure 5, 521–532.

10. Garrett, D.S., Kuszewski, J., Hancock, T.J., Lodi, P.J., Vuister, G.W., Gronenborn, A.M. & Clore, G.M. (1994) J. Magn. Reson. 104, 99–103.

11. Kuszewski, J., Qin, J., Gronenborn, A.M. & Clore, G.M. (1995) J. Magn. Reson. 106, 92–96.

12. Kuszewski, J., Gronenborn, A.M. & Core, G.M. (1995) J. Magn. Reson. 107, 293–297.

13. Kuszewski, J., Gronenborn, A.M. & Clore, G.M. (1996) J. Magn. Reson. 112, 79–81.

14. Kuszewski, J., Gronenborn, A.M. & Clore, G.M. (1996) Protein Sci. 5, 1067–1080.

15. Kuszewski, J., Gronenborn, A.M. & Clore, G.M. (1997) J. Magn. Reson. 125, 171–177.

16. Tjandra, N., Garrett, D.S., Gronenborn, A M., Bax, A & Clore, G.M. (1997) Nat. Struct. Bioi. 4, 443–449.

17. Tjandra, N., Omichinski, J.G., Gronenborn, A.M., Clore, G.M. & Bax, A. (1997) Nat. Struct. Biol. 4, 732–738.

18. Clore, G.M., Gronenborn, A.M. & Tjandra, N. (1998) J. Magn. Reson., 131, 159–162.

19. Clore, G.M. & Gronenborn, A.M. (1989) CRC Crit. Rev. Biochem. Biol. Biol. 24, 479–564.

20. Clore, G.M., Brünger, A.T., Karplus, M. & Gronenborn, A.M. (1986) J. Mol. Biol. 191, 523–551.

21. Nilges, M., Clore, G.M. & Gronenborn, A.M. (1988) FEBS Lett. 229, 317–324.

22. Stein, E.G., Rice, L.M. & Brünger, A.T. (1997) J. Magn. Reson. 124, 154–164.

23. Havel, T.F. & Wuthrich, K. (1985) J. Mol. Biol l82, 381–394.

24. Braun, W. (1987) Q. Rev. Biophys. 19, 115–157.

25. Gronenborn, A.M. & Clore, G.M. (1995) CRC Crit. Rev. Biochem. Mol. Biol. 30, 351–385.

26. Clore, G.M., Robien, M.A. & Gronenborn, A.M. (1993) J. Mol. Biol. 231, 81–102.

27. Bartik, K., Dobson, C.M. & Redfield, C. (1993) Eur. J. Biochem. 215, 255–266.

28. Wang, A.C. & Bax, A. (1996) J. Am. Chem. Soc. 118, 2483–2494.

29. Luzzati, V. (1952) Acta Crystalhgr. 5, 802–810.

30. Borgias, B.A., Gochin, M., Kerwood, D.J. & James, T.L. (1990) Progr. NMR Spectrosc. 22, 83–100.

31. Yip, P. & Case, D.A. (1991) J. Magn. Reson. 83, 643–648.

32. Nilges, M., Habbazettl, P., Brünger, A.T. & Holak, T.A. (1991) J. Mol. Biol. 219, 499–510.

33. Brünger, A.T., Clore, G.M., Gronenborn, A.M., Saffrich, R. & Nilges, M. (1993) Science 261, 328–331.

34. Karplus, M. (1963) J. Am. Chem. Soc. 85, 2870.

35. Bax, A., Vuister, G.W., Grzesiek, S., Delaglio, F., Wang, A.C., Tschudin, R. & Zhu, G. (1994) Methods Enzymol. 239, 79–106.

36. Hu, J.-S. & Bax, A. (1996) J. Am. Chem. Soc. 118, 8170–8171.

37. Ottiger, M. & Bax, A. (1997) J. Am. Chem. Soc. 119, 8070–8075.

38. Spera, S. & Bax, A. (1991) J. Am. Chem. Soc. 113, 5491–5492.

39. Wishart, D.S. & Sykes, B.D. (1994) J. Biomol NMR 4, 171–180.

40. Oldfield, E. (1995) J. Biomol. NMR 5, 217–225.

41. Osapay, K.A. & Case, D.A. (1991) J. Am. Chem. Soc. 113, 9436–9444.

42. Williamson, M.P. & Asakura, T. (1993) J. Magn. Reson. 101, 63–71.

43. Omichinski, J.G., Pedone, P.V., Felsenfeld, G., Gronenborn, A.M. & Clore, G.M. (1997) Nat. Struct. Biol. 4, 122–132.

44. Huth, J.R., Bewley, C.A., Nissen, M.S., Evans, J.N.S., Reeves, R., Gronenborn, A.M. & Core, G.M. (1997) Nat. Struct. Biol. 4, 657–665.

45. Lodi, P.J., Ernst, J.A., Kuszewski, J., Hickman, A.B., Engelman, A., Craigie, R., Clore, G.M. & Gronenborn, A.M. (1995) Biochemistry 34, 9826–9833.

46. Tjandra, N. & Bax, A (1997) Science 278, 1111–1114.

47. Woessner, D.E, (1962) J. Chem. Phys. 36, 647–654.

48. Bothner-By, A.A. (1995) in Encyclopedia of Nuclear Magnetic Resonance, eds. Grant. D.M. & Harris, R.K. (Wiley, Chichester, U.K.), pp. 2932–2938.

49. Tjandra, N., Grzesiek, S. & Bax, A. (1996) J. Am. Chem. Soc. 118, 6264–6272.

50. Kleywegt, G.J. & Jones, T.A (1997) Methods Enzymol 227, 208–230.

51. Clore, G.M., Ernst, J.A, Clubb, R.T., Omichinski, J.G., Kennedy, W.M.P., Sakaguchi, K., Appella, E. & Gronenborn, A.M. (1995) Nat. Struct. Biol. 2, 321–332.

52. Clore, G.M. & Gronenborn, A.M. (1991) J. Mol Biol. 217, 611–620.

53. Szyperski, T., Güntert, P., Stone, S.R. & Wüthrich, K. (1992) J. Mol. Biol. 228, 1192–1205.

54. Berndt, K.D., Günter, P., Orbons, L.P.M. & Wüthrich, K. (1992) J. Mol Biol. 227, 757–775.

55. Hyberts, S.G., Goldberg, M.S., Havel, T.F. & Wagner, G. (1992) Protein Sci. 1, 736–751.

56. Moore, J.M., Lepre, C., Gippert, G.P., Chazin, W.J., Case, D.A. & Wright, P.E. (1991) J. Mol Biol. 221, 533–555.

57. Billeter, M., Kline, A.D., Braun, W., Huber, R. & Wüthrich, K. (1989) J. Mol Biol. 206, 677–687.

58. Folkers, P.J. M., Clore, G.M., Driscoll, P.C., Dodt, J., Köhler, S. & Gronenborn, A.M. (1989) Biochemistry 28, 2601–2617.

59. Spitzfaden, C., Braun, W., Wider, G., Widmer, H. & Wüthrich, K. (1994) J. Biomol. NMR 4, 463–482.

60. Osapay, K., Theriault, Y., Wright, P.E. & Case, D.A (1994) J. Mol. Biol. 244, 183–197.

61. Clore, G.M., Gronenborn, A.M., Nilges, M. & Ryan, C.A. (1987) Biochemistry 26, 8012–8023.

62. Billeter, M., Vendrell, J., Wider, G., Aviles, F.X., Coll, M., Guasch, A., Huber, R. & Wüthrich, K. (1992) J. Biomolec. NMR 2, 1–10.

63. Clore, G.M., Gronenborn, A.M., James. M.N.G., Kjaer, M., McPhalen, C.A. & Poulsen. F.M. (1987) Protein Eng. 1, 313–318.



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